Pasado y presente en la terapia inmunosupresora de la nefritis lúpica en la provincia de Málaga

La Nefritis Lúpica (NL) es la afectación orgánica más frecuente y grave del Lupus. El tratamiento de inducción de remisión con Ciclofosfamida (Cf) ha sido considerado como primera opción históricamente por su eficacia, aunque, al presentar importantes efectos secundarios, la tendencia actual es la reducción de dosis o la búsqueda de diferentes estrategias como el Micofenolato (MMF), comenzando en los años noventa a introducirse en el mundo de la NL. El presente estudio pretende conocer los resultados en supervivencia global y renal y en seguridad, de una amplia serie de pacientes con NL grave y tratados en primera opción con CFiv ó MMF. Resultados: se realizaron 135 biopsias de 144 pacientes, clasificadas como tipo II una (0.7%), tipo III 25 (17%), tipo IV 79 (55%) y tipo V 30 (21%). En el grupo A (Cf mensual 24 m) se incluyeron 36 pacientes, en el B (Cf mensual 6 m + trimestral 18m) 61, el C (CF trimestral) y el D (MMF) 26. La supervivencia del grupo total (Kaplan-Meier, KM) a los 5, 10,15 y 20 años fue del 92, 87, 80 y 80% respectivamente. En el multivariante de Cox, la edad al diagnóstico de la nefritis (Hazard Ratio 1.05) y la supervivencia renal (HR 1.55) prevalecen como factores predoctores de mortalidad. La supervivencia renal (KM) a los 2, 5, 10, 15 y 20 años, fue del 94%, 91.2%, 80.7%, 67.1% y 61.5%, respectivamente. En el multivariante de Cox, se mantienen en el modelo final las variables creatinina basal (HR 1.30) y la remisión completa a los 24 meses (HR 0.23). No se encontraron diferencias significativas entre los cuatro grupos de tratamiento en los resultados de supervivencia global o renal. Los tratamientos administrados fueron también similares en lograr la normalización de los parámetros de función renal y actividad en los primeros 6 meses, permaneciendo dicha normalización estable hasta los 24m. En conjunto, se consiguió una exitosa tasa de remisión precoz a los 6 meses de 55-73% y a los 24 de 71-88%, sin diferencias entre grupos. La incidencia de neoplasias, infecciones y toxicidad ovárica fue baja y similar a la de estudios publicados previamente, relacionándose la toxicidad gonadal con la dosis de Cf

Glomerulonefritis colapsante con marcadores de desdiferenciación podocitaria en síndrome hemofagocítico secundario a linfoma hepatoesplénico de células T

El síndrome hemofagocítico es una condición clínica e histológica grave, secundaria a diferentes procesos. La glomerulonefritis colapsante es una podocitopatía proliferativa, generalmente de pronóstico desfavorable para la función renal. Se presenta un caso en el que las dos condiciones aparecieron asociadas, lo cual es una forma infrecuente de presentación del linfoma hepatoesplénico de células T. Se discute, asimismo, el papel de los marcadores de desdiferenciación podocitaria en esta glomerulopatía, y se revisan la fisiopatología y el tratamiento

A comprehensive database for integrated analysis of omics data in autoimmune diseases

This work is partially funded by FEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento (Grant CV20-36723), Consejeria de Salud (Grant PI-0173-2017) and by EU/EFPIA Innovative Medicines Initiative Joint Undertaking PRECISESADS (115565). JMM is partially funded by Ministerio de Economia, Industria y Competitividad. None of the funding bodies played any role in the design of the study and collection, analysis, and interpretation of data nor in writing the manuscript.Background: Autoimmune diseases are heterogeneous pathologies with difficult diagnosis and few therapeutic options. In the last decade, several omics studies have provided significant insights into the molecular mechanisms of these diseases. Nevertheless, data from different cohorts and pathologies are stored independently in public repositories and a unified resource is imperative to assist researchers in this field. Results: Here, we present Autoimmune Diseases Explorer (https:// adex. genyo. es), a database that integrates 82 curated transcriptomics and methylation studies covering 5609 samples for some of the most common autoimmune diseases. The database provides, in an easy-to-use environment, advanced data analysis and statistical methods for exploring omics datasets, including meta-analysis, differential expression or pathway analysis. Conclusions: This is the first omics database focused on autoimmune diseases. This resource incorporates homogeneously processed data to facilitate integrative analyses among studies.FEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento CV20-36723Consejeria de Salud PI-0173-2017EU/EFPIA Innovative Medicines Initiative Joint Undertaking PRECISESADS 115565Ministerio de Economia, Industria y Competitivida

Risk factors for non-diabetic renal disease in diabetic patients

Background. Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes. Methods. Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. Results. In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 6 12.8 years, creatinine was 2.8 6 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2–5.4) g/24 h. About 39.5% (n ¼ 329) of patients had DN, 49.6% (n ¼ 413) NDRD and 10.8% (n ¼ 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n ¼ 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) ¼ 1.03, 95% CI: 1.02–1.05, P < 0.001], microhaematuria (OR ¼ 1.51, 95% CI: 1.03–2.21, P ¼ 0.033) and absence of diabetic retinopathy (DR) (OR ¼ 0.28, 95% CI: 0.19–0.42, P < 0.001) were independently associated with NDRD. Kaplan–Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P ¼ 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P ¼ 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P ¼ 0.002), higher creatinine (P ¼ 0.01) and DN (P ¼ 0.015) were independent risk factors for mortality. Conclusions. The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis

A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer

Funder: Fundación Científica Asociación Española Contra el Cáncer (ES)Funder: Cancer Focus Northern Ireland and Department for Employment and LearningFunder: Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, USAAbstract: Background: Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance. Methods: We complemented a new conventional PC GWAS (1D) with genome spatial autocorrelation analysis (2D) permitting to prioritize low frequency variants not detected by GWAS. These were further expanded via Hi-C map (3D) interactions to gain additional insight into the inherited basis of PC. In silico functional analysis of public genomic information allowed prioritization of potentially relevant candidate variants. Results: We identified several new variants located in genes for which there is experimental evidence of their implication in the biology and function of pancreatic acinar cells. Among them is a novel independent variant in NR5A2 (rs3790840) with a meta-analysis p value = 5.91E−06 in 1D approach and a Local Moran’s Index (LMI) = 7.76 in 2D approach. We also identified a multi-hit region in CASC8—a lncRNA associated with pancreatic carcinogenesis—with a lowest p value = 6.91E−05. Importantly, two new PC loci were identified both by 2D and 3D approaches: SIAH3 (LMI = 18.24), CTRB2/BCAR1 (LMI = 6.03), in addition to a chromatin interacting region in XBP1—a major regulator of the ER stress and unfolded protein responses in acinar cells—identified by 3D; all of them with a strong in silico functional support. Conclusions: This multi-step strategy, combined with an in-depth in silico functional analysis, offers a comprehensive approach to advance the study of PC genetic susceptibility and could be applied to other diseases

Efficient Wireless Monitoring and Control of a Grid-Connected Photovoltaic System

The design, monitoring, and control of photovoltaic (PV) systems are complex tasks that are often handled together, and they are made even more difficult by introducing features such as real-time, sensor-based operation, wireless communication, and multiple sensor nodes. This paper proposes an integrated approach to handle these tasks, in order to achieve a system efficient in tracking the maximum power and injecting the energy from the PV modules to the grid in the correct way. Control is performed by means of an adaptive Lyapunov maximum power point tracking (MPPT) algorithm for the DC/DC converters and a proportional integral (PI) control for the inverters, which are applied to the system using low latency wireless technology. The system solution exploits a low-cost wireless multi-sensor architecture installed in each DC/DC converter and in each inverter and equipped with voltage, current, irradiance, and temperature sensors. A host node provides effective control, management, and coordination of two relatively independent wireless sensor systems. Experimental validation shows that the controllers ensure maximum power transfer to the grid, injecting low harmonic distortion current, thus guaranteeing the robustness and stability of the system. The results verified that the MPPT efficiency is over 99%, even under perturbations and using wireless communication. Moreover, the converters’ efficiency remains high, i.e., for the DC/DC converter a mean value of 95.5% and for the inverter 93.3%